Intrahepatic cholesterol influences progression, inhibition and reversal of non-alcoholic steatohepatitis in hyperlipidemic mice
Open accessAbstract
Hepatic inflammation is the key factor in non‐alcoholic steatohepatitis (NASH) and promotes progression to liver damage. We recently identified dietary cholesterol as the cause of hepatic inflammation in hyperlipidemic mice. We now show that hepatic transcriptome responses are strongly dependent on cholesterol metabolism during diet‐induced NASH and its inhibition by fenofibrate. Furthermore, we show that, despite doubling hepatic steatosis, pharmacological LXR activation reverses hepatic inflammation, in parallel with reversing hepatic cholesterol levels. Together, the results indicate a prominent role of cholesterol during the development, inhibition and reversal of hepatic inflammation in NASH and reveal potential new therapeutic strategies against NASH.
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LXR activation improves hepatic inflammation and reduces liposaccharides-induced liver injury in NASH mouse models.
“LXR activation has been shown to improve hepatic inflammation and reduce liposaccharides-induced liver injury in NASH mouse models [126,127,128].”
From GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives (2023) · cites this paper as [126]
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References 31 · Cited by 109
- Authors
- Wouters, K., van Bilsen, M., van Gorp, P. J., Bieghs, V., Lütjohann, D., Kerksiek, A., Staels, B., Hofker, M. H., & Shiri-Sverdlov, R.
- Affiliations
- Maastricht University (NL)
- University of Bonn (DE)
- Inserm (FR)
- University Medical Center Groningen (NL)
- Corresponding author
- Wouters, Kristiaan
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2010-01-28
- Volume
- 584
- Issue
- 5
- Pages
- 1001-1005
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2121509986
- Cited by
- 109
- References
- 31
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 12 · 2022: 10 · 2021: 6 · 2020: 6 · 2019: 11 · 2018: 7 · 2017: 5 · 2015: 9 · 2014: 8 · 2013: 5 · 2012: 6
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Dutch Heart Foundation (2002B18)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- nonalcoholic steatohepatitis, liver inflammation, hyperlipidemia, fenofibrate, liver X receptor, cholesterol metabolism, liver transcriptome, hepatic steatosis, diet-induced NASH
- MeSH terms
- Animals, Cholesterol, Dietary Fats, Disease Models, Animal, Fatty Liver, Gene Expression Regulation, Liver, Mice, Mutant Strains, Mice
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